During fiscal year 2008 we accomplished the following:[unreadable] [unreadable] We have previously proposed that the timing of activation-induced cell death of CD4 T cells stimulated via the T cell receptor (TCR) is determined by the kinetics of NF-&#954;B up- and down-regulation. To strengthen, or refute, this idea we have sought ways to alter the duration of NF-&#954;B signaling in these cells and to identify possible NF-&#954;B gene targets that regulate cell death. Towards these goals we found that:[unreadable] [unreadable] (1) CD4+ T cells activated via the TCR as well as TNF&#945; maintain nuclear NF-&#954;B for longer duration. Apoptosis occurs in TNF&#945; plus TCR stimulated cells later as predicted by our model.[unreadable] [unreadable] (2) One NF-&#954;B target gene that affected cell viability was COX-2. We demonstrated that this gene is induced in response to TCR stimulation and its inhibition leads to increased cell death.[unreadable] [unreadable] (3) We confirmed that this form of death is mediated via death receptors by performing the studies with CD4+ T cell blasts from Fas-deficient lpr mice. [unreadable] [unreadable] (4) For NF-&#954;B effects to be transient, mRNAs of genes activated must be short lived. This prediction was tested by isolating RNA from cells treated for various times with actinomycin D starting at the peak of NF-&#954;B activity. Analysis by quantitative RT-PCR demonstrated that several known NF-&#954;B target genes had short mRNA half-life. These RNA samples are being examined at a more global level by hybridization to oligonucleotide arrays.